Oral pharmacokinetics and ascitic fluid penetration of pefloxacin in cirrhosis

Cardey, J.; Silvain, Christine; Bouquet, S.; Breux, J. P.; Becq‐Giraudon, B.; Fourtillan, J. P.; Beauchant, Michel

doi:10.1007/bf00544237

Cited by 32 publications

(5 citation statements)

References 32 publications

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“…The mean tissue/serum ratios concentrations were 1 and 2.3 for pefloxacin and norfloxacin respectively. The good penetration into the uroepithelium observed with pefloxacin agrees with the results reported in the literature for body fluids and tissues (the ascitic fluids [11], the epididymis [8], the prostatic tissue [7], the heart valves [12], diffusion of pefloxacin, and the penetration of norfloxacin into the urogenital tract tissue [13]). The two compounds have a strong lipophilicity; the distribution coefficient of the N-desmethyl derivative (0.04) is higher than those of the parent drug (0.03) [14].…”

Section: Discussionsupporting

confidence: 91%

Penetration of pefloxacin and its desmethyl metabolite into the uroepithelium after a 800-MG single oral dose in human patients

Lozniewski

et al. 1996

Eur J Clin Pharmacol

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Penetration of pefloxacin into the uroepithelium was studied in 20 patients (10 men and 10 women) receiving a single oral dose of 800 mg. Samples of serum, urine, and uroepithelium were taken 1.8 h (mean) after the dose. Pefloxacin and its active metabolite, norfloxacin, were assayed by liquid chromatography, and the microbiologically active compounds were quantified by a microbiological assay. Both procedures were correlated (r > 0.7); nevertheless, slight differences detected in concentrations depended on the levels of norfloxacin achieved in the biological samples. The serum and tissue concentrations were higher than the concentration of bactericide (4 micrograms.ml-1), except in one case. The uroepithelium concentration of pefloxacin was proportional to the serum concentration (r = 0.79). The urinary concentrations ranged from 1.2 micrograms.ml-1 to 82.4 micrograms.ml-1. The mean norfloxacin/pefloxacin ratios were 3% in serum, 8% in uroepithelium, and 44% in urine. The mean uroepithelium/serum concentration ratios were 1 for pefloxacin and 2.3 for norfloxacin. This result shows that, at a time close to that of the maximum concentration, there is good penetration of pefloxacin and norfloxacin into the uroepithelium.

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Section: Discussionsupporting

confidence: 91%

Penetration of pefloxacin and its desmethyl metabolite into the uroepithelium after a 800-MG single oral dose in human patients

Lozniewski

et al. 1996

Eur J Clin Pharmacol

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“…The investigators stated that the dosage of pefloxacin should be modified in these patients. Similar results are reported by Cardey et al (1987). In addition, the investigators stressed the pronounced accumulation of pefloxacin in plasma and ascitic fluid after repeated administration and advocated a reduced dosage in these patients.…”

Section: Vz/fsupporting

confidence: 83%

Clinical Pharmacokinetics of Newer Antibacterial Agents in Liver Disease

Westphal

1993

Clinical Pharmacokinetics

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Liver disease may produce significant, albeit highly variable, effects on the pharmacokinetic behaviour of antibiotics in serum. Drug disposition may be altered through several pathophysiological mechanisms including reduced hepatobiliary clearance, and modifications in the volume of distribution induced by albumin synthesis deficiency or portal hypertension-related ascites. Antibacterial agents are not affected by potential alteration in hepatic first-pass effects. Only liver cirrhosis-induced effects on serum pharmacokinetics of antibiotics have been extensively studied, unlike those possibly produced by other forms of liver disease. In liver cirrhosis, pharmacokinetic alterations of nearly all beta-lactam or quinolone agents appear not to be marked enough to require dosage adjustment, provided that renal function stays normal. Adaptation in therapeutic schedule, however, is warranted for those drugs that are substantially cleared by the hepatobiliary system, namely mezlocillin, clindamycin, erythromycin, pefloxacin, enoxacin, antituberculous agents or nitroimidazole derivatives. Special caution should also be exercised when using aminoglycosides or vancomycin because of the wide interpatient variability of their pharmacokinetic disposition and their toxic potential. When renal function is impaired and there is an increased volume of distribution due to ascites, as frequently observed in severe liver insufficiency, the elimination half-life of most antibiotics is markedly prolonged, resulting in potential side effects due to drug accumulation. Accordingly, dosage adjustment applies to all drugs. In this regard, it should be remembered that delineating the dosage guidelines for a given antibiotic on the basis of reported pharmacokinetic parameters in patients with liver cirrhosis is awkward and probably of limited value. This pattern is ascribed to large interpatient variability in the active hepatic cell mass, the degree of portal hypertension and the alteration of serum binding capacity. Furthermore, there is no way of predicting accurately the extent of liver insufficiency in an individual patient. Dosage reduction is thus done empirically in most cases. Whenever possible, direct measurements of serum antibiotic concentrations should be the reasonable approach to manage antibiotic therapy in this kind of clinical condition.

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“…Cardley et al [28] and Galtier et al [39] stressed the importance of the accumulation of pefloxacin after repeated administration. Moreover, in the results reported by Galtier et al, [39] a practical tool is proposed for estimating the most likely values of pharmacokinetic parameters for a given patient, taking into account the values of the Child-Pugh score or the prothrombin time ( fig.…”

Section: Hepatic Dysfunctionmentioning

confidence: 98%

Pefloxacin Clinical Pharmacokinetics

Bressolle

Gonçalves

Gouby

et al. 1994

Clinical Pharmacokinetics

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Pefloxacin has a broad spectrum of activity against a great number of Gram-negative and Gram-positive bacteria. It is also capable of penetration into cells, yielding high tissue:serum ratios, with implications for the treatment of infections caused by intracellular pathogens. Pefloxacin is well absorbed from the gastrointestinal tract. Its elimination half-life ranges from 6.2 to 12.4 hours. After repeated administration, a major change in pharmacokinetic parameters is observed. Pharmacokinetic parameters are minimally altered or not altered in patients with impaired renal function. Altered plasma pharmacokinetics in patients with liver insufficiency and in elderly patients are observed, so dosage adjustments are necessary. In addition, pefloxacin interacts with a number of other compounds at hepatic (e.g. theophylline and cimetidine) and gastrointestinal (e.g. antacids) sites. With the exception of saliva, cerebrospinal fluid, aqueous humor, vitreous fluid and amniotic fluid, body fluid concentrations reach plasma concentrations. Studies on tissue penetration show that concentrations exceeding plasma concentrations are obtained in most tissues. The highest tissue:plasma concentration ratios are achieved in lung and kidney, whereas concentrations in fat are considerably lower than those in plasma.

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Oral pharmacokinetics and ascitic fluid penetration of pefloxacin in cirrhosis

Cited by 32 publications

References 32 publications

Penetration of pefloxacin and its desmethyl metabolite into the uroepithelium after a 800-MG single oral dose in human patients

Penetration of pefloxacin and its desmethyl metabolite into the uroepithelium after a 800-MG single oral dose in human patients

Clinical Pharmacokinetics of Newer Antibacterial Agents in Liver Disease

Pefloxacin Clinical Pharmacokinetics

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